A limited role for PI(3,4,5)P3 regulation in controlling skeletal muscle mass in response to resistance exercise

D. Lee Hamilton, Andrew Philp, Matthew G. MacKenzie, Keith Baar

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Background: Since activation of the PI3K/(protein kinase B; PKB/akt) pathway has been shown to alter muscle mass and growth, the aim of this study was to determine whether resistance exercise increased insulin like growth factor (IGF) I/ phosphoinositide 3-kinase (PI3K) signalling and whether altering PI(3,4,5)P3 metabolism genetically would increase load induced muscle growth. Methodology/Principal Findings: Acute and chronic resistance exercise in wild type and muscle specific PTEN knockout mice were used to address the role of PI(3,4,5)P3 regulation in the development of skeletal muscle hypertrophy. Acute resistance exercise did not increase either IGF-1 receptor phosphorylation or IRS1/2 associated p85. Since insulin/IGF signalling to PI3K was unchanged, we next sought to determine whether inactivation of PTEN played a role in load-induced muscle growth. Muscle specific knockout of PTEN resulted in small but significant increases in heart (PTEN+/+ = 5.00±0.02 mg/g, PTEN-/- = 5.50±0.09 mg/g), and TA (PTEN+/+ = 1.74±0.04 mg/g, PTEN-/- = 1.89 ±0.03) muscle mass, while the GTN, SOL, EDL and PLN remain unchanged. Following ablation, hypertrophy of the PLN, SOL or EDL muscles was similar between PTEN-/- and PTEN+/+ animals. Even though there were some changes in overload-induced PKB and S6K1 phosphorylation, 1 hr following acute resistance exercise there was no difference in the phosphorylation state of S6K1 Thr389 between genotypes. Conclusions/Significance: These data suggest that physiological loading does not lead to the enhanced activation of the PI3K/PKB/mTORC1 axis and that neither PI3K activation nor PTEN, and by extension PI(3,4,5)P3 levels, play a significant role in adult skeletal muscle growth.

Original languageEnglish (US)
Article numbere11624
JournalPLoS One
Volume5
Issue number7
DOIs
StatePublished - Jul 16 2010

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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